Regulation of Xenopus Embryonic Development by TGFbeta Superfamily Ligands and SMADs

We are studying how members of the TGFß superfamily act to exert a wide range of cell-type specific actions during development.  Our current focus is on the role of TGFß ligands and their major signal transducers, the Smads, in two sets of developmental events:  1) the regulation of migration of cell populations that establish the craniofacial skeleton and the body wall musculature; 2) the normal growth of the tail and the regeneration of this structure following surgical extirpation. Migration of cell populations over extended distances in the embryo prior to their terminal differentiation is a critical component of the establishment of embryonic pattern. These migrations involve cell behaviors and regulatory programs that may be recapitulated during tumor metastasis, making an understanding of their regulation important for tumor biology as well as embryology. The craniofacial skeleton is made up primarily of neural crest cells that migrate from the edge of the anterior neural plate into the craniofacial region, where they differentiate into cartilage and bone; the muscle of the body wall is made up of muscle precursor cells that migrate from the somites to the ventro-lateral body wall, where they differentiate into muscle.  Preliminary experiments implicate BMP signals as regulators of these migrations or subsequent differentiation; we will use a novel conditional inhibitor to understand how BMPs regulate these processes. The Xenopus tail has been shown to be a powerful system for the study of the molecular basis of complex regenerative events. We shown that TGFß signaling is essential for regeneration of nerve, muscle, and notochord in regenerating tissues, and is necessary for multiple distinct steps in the regeneration process. We plan to further define how TGFß signaling participates in the establishment and maintenance of a regeneration program.